The ability to monitor and control neuronal ensembles has far reaching impact on public health ranging from a fundamental understanding of cognitive disabilities to active control of paralyzed limbs. State-of-the-art neuronal probes are based on stiff ceramic and metallic materials that demonstrate poor long-term biocompatibility with soft brain tissue and moderate electrical recording properties. These shortcomings circumvent the possibility of chronic measurements necessary for studying or modifying the neural basis of behavior in awake-behaving animals. The vision of this Exploratory/Developmental Award (R21) application is to develop neuronal probes demonstrating long-term biocompatibility based on emerging polymer materials and state-of-the-art fabrication technologies. The specific objective of the work is to develop a chronic neuronal probe using microwires with optimal electrical recording properties encapsulated within a tailored biocompatible polymer delivery structure. Multifunctional properties of the polymer sheath, e.g. shape memory capacity and biodegradability, will be used to explore advanced probe design concepts such as self-insertion and vanishing insertion tethers, both of which should improve long-term biocompatibility and facilitate high-fidelity chronic neuronal measurements. The proposed polymer neuronal probes should have broad impact on probe technology by providing a platform for future tissue engineered probes capable of cell scaffolding and controlled release of therapeutic drugs. The two specific aims of the proposed work are designed to eliminate the most significant barriers to the development of polymer neuronal probes; small-scale fabrication, mechanical insertability, and biocompatibility assessment. In Aim 1, two-photon stereolithography will be used to fabricate gold microwire encapsulated polymer probes with various designs. In Aim 2, the local and global mechanical properties of the probes will be assessed using in-vitro nanoindentation and in-vivo insertion tests into a mouse olfactory bulb. Short and long term biocompatibility of the probes will be assessed using the mouse olfactory bulb model. Multifunctional self-deployment and biodegradation studies will also be conducted on the probes using similar in-vitro and in-vivo approaches. [unreadable] [unreadable] [unreadable]